1. Field of the Invention
This invention relates to the field of microfluidic devices. More particularly, this invention relates to a multilayered microfluidic device, formed from layers of greensheet, having components that are co-fired with and sintered to the green-sheet layers to provide an integrated and monolithic structure and also relates to methods for making such devices.
2. Description of Related Art
Microfluidic devices have a wide variety of chemical and biological applications. Specifically, microfluidic devices can be used to mix, react, meter, analyze, and detect chemicals and biological materials in a fluid state. Many synthetic and analytical techniques that conventionally require large, bulky, and complicated apparatus can be miniaturized as microfluidic devices.
Microfluidic devices are most commonly made from silicon, glass, or plastic substrates. However, each of these materials has certain disadvantages that limit its utility. Channels and various other microfluidic structures may be etched into silicon, but such etching processes are not typically able to form the complex three-dimensional structures and embedded structures that are often desirable in microfluidic devices. Silicon, as a material, is also not compatible with many fluids containing biological materials. Typically, this problem is overcome by the additional step of applying a special coating to the microfluidic channels. Finally, because silicon is a semiconductor, certain pumping techniques, such as electrohydrodynamic pumping and electroosmotic pumping, are difficult or impossible to achieve. Overall, silicon is an expensive substrate to work with, making it of only limited use for the large scale production of microfluidic devices that typically do not require structures with dimensions less than about 10 microns.
Like silicon, channels may also be etched into glass substrates. Although three-dimensional and embedded structures can be built up by bonding together successive layers of glass, using an anodic bonding process, this bonding process is difficult and very costly. In particular, each layer is added sequentially, i.e., only one at a time. Moreover, the surface of each successive layer must be nearly perfectly flat in order to achieve reliable bonding. This stringent flatness requirement makes the fabrication of multilayered glass devices difficult and expensive and results in low yields.
Plastic also has a number of disadvantages as a substrate for microfluidic devices. First, most types of plastic substrate cannot be used above about 350xc2x0 C., thereby limiting the extent to which plastic microfluidic devices can heat fluids. Second, many plastic materials, like silicon, have biocompatibility problems. Accordingly, biocompatibility is typically achieved by the additional step of adding special coatings to the fluid passageways. Third, it is believed that, like silicon, electroosmotic pumping would be difficult or impossible to achieve in plastic microfluidic devices because of the lack of available fixed surface charge. Fourth, the ability to fabricate three-dimensional and embedded structures in plastic devices is limited because it is be difficult to join more than two plastic layers together.
In a first principal aspect, the present invention provides a multilayered microfluidic device comprising a substantially monolithic structure formed from a plurality of green-sheet layers sintered together, wherein the green-sheet layers include particles selected from the group consisting of ceramic particles, glass particles, and glass-ceramic particles. The substantially monolithic structure has a fluid passageway defined therein. The fluid passageway has an inlet port for receiving fluid, an outlet port for releasing a fluid, and an interconnection between the inlet port and the outlet port. The substantially monolithic structure also has an electrically conductive pathway defined therein, at least a portion of which is formed by sintering a thick-film paste to at least one of the green-sheet layers.
In a second principal aspect, the present invention provides a multilayered microfluidic device comprising a substantially monolithic structure formed from a plurality of green-sheet layers sintered together, wherein the green-sheet layers include particles selected from the group consisting of ceramic particles, glass particles, and glass-ceramic particles. The substantially monolithic structure has a fluid passageway defined therein. The fluid passageway has an inlet port for receiving fluid, an outlet port for releasing a fluid, and an interconnection between the inlet port and the outlet port. A fluid sensor for sensing fluid in a portion of the fluid passageway is sintered to at least one of the green-sheet layers so as to be integral with the substantially monolithic structure.
In a third principal aspect, the present invention provides a multilayered microfluidic device comprising a substantially monolithic structure formed from a plurality of green-sheet layers sintered together, wherein the green-sheet layers include particles selected from the group consisting of ceramic particles, glass particles, and glass-ceramic particles. The substantially monolithic structure has a fluid passageway defined therein. The fluid passageway has an inlet port for receiving fluid, an outlet port for releasing a fluid, and an interconnection between the inlet port and the outlet port. A fluid motion transducer for converting electrical energy into fluid motion in a portion of the fluid passageway is sintered to at least one of the green-sheet layers so as to be integral with the substantially monolithic structure.
In a fourth principal aspect, the present invention provides a multilayered microfluidic device comprising a substantially monolithic structure formed from a plurality of green-sheet layers sintered together, wherein the green-sheet layers include particles selected from the group consisting of ceramic particles, glass particles, and glass-ceramic particles. The substantially monolithic structure has a fluid passageway defined therein. The fluid passageway has an inlet port for receiving fluid, an outlet port for releasing a fluid, and an interconnection between the inlet port and the outlet port. The substantially monolithic structure also includes an optically transmissive portion for providing external optical access to a portion of the fluid passageway.
In a fifth principal aspect, the present invention provides a multilayered microfluidic device comprising a substantially monolithic structure formed from a plurality of green-sheet layers sintered together, wherein the green-sheet layers include particles selected from the group consisting of ceramic particles, glass particles, and glass-ceramic particles. The substantially monolithic structure has a fluid passageway defined therein. The fluid passageway has an inlet port for receiving fluid, an outlet port for releasing a fluid, an interconnection between the inlet port and the outlet port, and includes a cavity. The substantially monolithic structure also includes means for lysing. cells in the cavity.
In a sixth principal aspect, the present invention provides a method for making a multilayered microfluidic device. A plurality of green-sheet layers is textured in a first predetermined pattern defining a fluid passageway. The green-sheet layers include particles selected from the group consisting of ceramic particles, glass particles, and glass-ceramic particles. A thick-film paste is applied to the green-sheet layers in a second predetermined pattern defining a fluid-interacting component. The green-sheet layers are then sintered together at a predetermined temperature for a predetermined amount of time to form a substantially monolithic structure. The substantially monolithic structure has the fluid passageway and the fluid-interacting component defined therein.
In a seventh principal aspect, the present invention provides a multilayered microfluidic device comprising a substantially monolithic structure formed from a plurality of green-sheet layers sintered together, wherein the green-sheet layers include particles selected from the group consisting of ceramic particles, glass particles, and glass-ceramic particles. The substantially monolithic structure has a fluid passageway defined therein. Disposed within the fluid passageway is a hydrophobic region sintered to one of the green-sheet layers.
Because the multilayered microfluidic devices of the present invention are made from a plurality of green-sheet layers sintered together, the devices may be provided with a wide variety of properties and functionalities useful for chemical and biological applications. The materials of the green-sheet layers may be chosen so as to be chemically and biologically compatible with the fluids used in the device and may also be chosen to be compatible with the particular range of temperature used in the device.
Additionally, the green-sheet layers in the device need not be all made of the same material. In this way, the device may be advantageously provided with different properties, such as thermal conductivity, in different locations. As an important example, one of the green-sheet layers may include glass particles, so as to provide an optically transmissive layer allowing external optical access to portions of the fluid passageways in the device.
By allowing each green-sheet layer to be processed individually before being sintered together, complicated structures may also be built into the devices of the present invention. For example, the fluid passageway in the device may be defined by structures, such as vias and channels, which are formed into several green-sheet layers before the layers are sintered together. Accordingly, the fabrication out of a plurality of layers allows the fluid passageway to have a complicated three-dimensional structure that would otherwise be difficult to achieve.
Green-sheet technology also allows the provision into the devices of a wide variety of functional components, such as heating elements, cooling elements, fluid sensors, and fluid motion transducers. Advantageously, these functional components may be co-fired with and sintered to the green-sheet layers so as to be integral with the device. Such integral components are more efficiently and reliably incorporated into the device, and, thus, facilitate large-scale manufacturing of microfluidic devices.
Thick-film technology is an important way of providing such integral components. Thick-film pastes may silk-screened onto individual green-sheet layers and then co-fired with and sintered to the green-sheet layers to become integral with the device. The thick-films may include conductive materials, such as metals, to provide electrically conductive pathways in the device. In particular, the use of conductive traces deposited onto the surfaces of green-sheet layers in combination with conductor-filled vias in the green-sheet layers allows for the efficient fabrication of complicated electrical conduction pathways in the device. Thick-film technology also allows other materials, such as thermoelectric, piezoelectric, and high magnetic permeability materials to be incorporated into the device.